Copolymers of L-glutamic acid, L-alanine, L-tyrosine, and L-lysine and mixtures thereof have long been known. (U.S. Pat. No. 3,849,550, issued Nov. 19, 1974 (Teitelbaum, et al.))
Over the last two decades such copolymer mixtures have been extensively studied, and numerous modifications as well as potential uses have been identified. As a result of these efforts, a commercial product, COPAXONE®, was developed which is now marketed.
Specifically, COPAXONE® is the brand name for a pharmaceutical composition which contains glatiramer acetate (GA) as the active ingredient. COPAXONE® contains the acetate salts of synthetic polypeptides, containing four naturally occurring amino acids: L-glutamic acid, L-alanine, L-tyrosine, and L-lysine with an average molar fraction of 0.141, 0.427, 0.095, and 0.338, respectively. The average molecular weight of glatiramer acetate is 4,700-11,000 daltons. Chemically, glatiramer acetate is designated L-glutamic acid polymer with L-alanine, L-lysine and L-tyrosine, acetate (salt). Its structural formula is:(Glu, Ala, Lys, Tyr)χ.χCH3COOH(C5H9NO4.C3H7NO2.C6H14N2O2.C9H11NO3)χ.χC2H4O2 CAS-147245-92-9(“Copaxone”, Physician's Desk Reference, (2000), Medical Economics Co., Inc., (Montvale, N.J.), 3115.)
Glatiramer acetate is approved for use in the reduction of the frequency of relapses in patients with relapsing-remitting multiple sclerosis. Multiple sclerosis has been classified as an autoimmune disease. Glatiramer acetate has also been disclosed for use in the treatment of other autoimmune diseases (Publication No. US 2002/0055466 A1 for R. Aharoni et al.), inflammatory non-autoimmune diseases (Publication No. US 2005/0014694 A1 for V. Wee Yong et al.; and U.S. Patent Application No. 2002/0077278 A1, published Jun. 20, 2002 (Young et al.)) and to promote nerve regeneration and/or to prevent or inhibit secondary degeneration which may follow primary nervous system injury (Publication No. US 2003/0004099 A1 for M. Eisenbach-Schwartz et al.; and U.S. Patent Application No. 2002/0037848 A1, published Mar. 28, 2002 (Eisenbach-Schwartz)). Furthermore, glatiramer acetate has been disclosed as a treatment for immune mediated diseases (e.g., U.S. Pat. No. 6,514,938 B1, issued Feb. 4, 2003 (Gad et al.); PCT International Publication No. WO 01/60392, published Aug. 23, 2001 (Gilbert et al.); and PCT International Publication No. WO 00/27417, published May 19, 2000 (Aharoni et al.) as well as diseases associated with demyelination (PCT International Publication No. WO 01/97846, published Dec. 27, 2001 (Moses et al.).
As a result of further study and improvement, a new mixture of such copolymers has been developed which has potential as a well-tolerated non-steroidal medication for the treatment of multiple sclerosis and other diseases as described more fully herein.